Medical Student Research Projects

Projects with Ophthalmology Faculty

Throughout the year, Department of Ophthalmology faculty members welcome medical student involvement in research projects. Medical students interested in pursuing research in the Department of Ophthalmology should review the topics below and contact the faculty member directly.

The rare retinal dystrophy, Malattia Leventinese, is caused by a mutation of an arginine residue at the 345th position in a protein called fibulin-3. Instead of incorporating an arginine residue, a change in the DNA code results in the insertion of a large, bulky tryptophan residue. This mutation site occurs in a specific region of the protein called an epidermal growth factor (EGF) domain. The presence of this large tryptophan residue causes problems with fibulin-3 protein folding and its eventual secretion from cells. As a result, the disease-causing mutant protein is poorly secreted and has a tendency to activate the cell’s stress responsive signaling pathways. However, it is unknown what would happen to fibulin-3 protein folding and secretion if we were to introduce a tryptophan mutation in other regions of the fibulin-3 protein. Would this tryptophan mutation be better tolerated in other similar, yet distinct EGF domains? Or does the presence of a tryptophan residue in any of the EGF domains have the same effect on fibulin-3 protein folding?

The goal of this project is to determine what happens to fibulin-3 secretion when we introduce similar, potentially pathogenic, tryptophan mutations in different EGF domains of the fibulin-3 protein.

Generation of high-throughput-capable fusion proteins for identifying new drugs to treat retinal diseases

A number of retinal disorders are caused by genetic mutations in genes encoding for secreted proteins. Many of these mutations compromise protein folding, and thus cause a defect in the protein’s secretion efficiency. Identifying compounds which rescue the mutant protein’s secretion defect is of substantial interest to my lab. However, since a cell at any given time secretes tens of thousands of proteins, it is difficult to specifically monitor the secretion of the one protein. Researchers have therefore developed reporter assays to follow a single protein by modifying it and making it unique compared to the rest of the cell’s proteome. One such reporter assay strategy is to fuse is a light-generating enzyme (luciferase) to the protein of interest. Then, using an assay to detect the amount light given off in a sample, researchers can infer how much protein of interest is present. Such an approach can be useful for identifying new potential drugs which rescue the secretion defects using unbiased screening techniques in a high-throughput manner.

The goal of this project will be to use the Gaussia luciferase or Nano luciferase as a way to follow the secretion of retinal disease-associated proteins. Following the successful establishment and validation of this assay, the student will perform small-scale high-throughput screening experiments to identify drugs which may rescue the secretion of the mutant protein.

The effect of clinical experience on personal thresholds for the diagnosis and treatment of glaucoma suspects

Early glaucoma can be difficult to diagnose. A number of glaucoma risk calculators have been designed to help quantify the risk of a patient developing glaucoma over the next five years based on specific risk factors. However, most ophthalmologists use their own experience rather than these calculators in deciding the treatment course of any particular patient.

The goal of this retrospective study is to determine whether resident physicians who have less experience than attending physicians have a lower or higher threshold for labeling patients as glaucoma suspects and for initiating glaucoma treatment. This data will be useful to ophthalmology residents looking for guidance in establishing their own personal thresholds for the diagnosis and treatment of glaucoma suspects.

Intravitreal and sub-Tenon’s steroid injections are useful for a number of ocular conditions including edema from diabetic retinopathy and retinal vein occlusions. However, use of these depot injections is hampered by the fear of inducing intractable glaucoma by steroid that cannot be removed once given. In contrast, the glaucoma induced by topical steroids is generally reversible once the drops are stopped. Although usually not useful as a treatment for posterior segment disease, topical steroids may serve as a useful test by which steroid-responsive individuals can be identified.

The goal of this retrospective study is to determine the positive and negative predictive values of topical steroid response for glaucoma induced by depot steroids. The patient population will include patients who were prescribed a course of topical steroids after pterygium excision and who subsequently underwent depot steroid injections for macular edema related to diabetes or retinal vein occlusion.

Vlad Matei, M.D. (PGY2)

Project: Retinal vein occlusions (RVO), which include central and branch retinal vein occlusions (CRVO and BRVO), are the second most common retinal vascular disorders after diabetic retinopathy and are a common source of visual loss. We do not yet have a good definitive treatment for RVOs, and there is hardly any literature on preventive measures. RVOs have several risk factors, and may have several pathophysiologic elements, in common with cardiovascular disease. Aspirin and statins are widely used for both the primary and secondary prevention of cardiovascular disease, but the role of these medications in RVOs has scarcely been studied. Since RVO is much more common in patients with a history of glaucoma and hypertension, we will limit our study population to those with both of these risk factors. We will compare the use of aspirin and statins separately in patients with hypertension and glaucoma who developed RVO versus in those who did not develop RVO, to see whether aspirin and statins may decrease the risk of RVO. This will be a retrospective case-control study, based on review of patient charts.

Responsibilities: To review patient charts, organize data into spreadsheets, help with data analysis, and co-author the manuscript. We—the medical student, the resident (Vlad Matei, M.D.), and the attending (Chan Nguyen, M.D.)—will work together on all of these aspects. Vlad Matei will provide the background reading materials to the student. Our goal will be a poster presentation and also a publication in a peer-reviewed journal, with the student as co-author.

Mohamed Guenena, M.D. (PGY2)

Project: A retrospective study on the value of ordering MRI in congenital or early onset nystagmus in children. We will look at our patients with nystagmus who had an MRI to see if any abnormalities were noted and to determine value/necessity of imaging in nystagmus patients.

Responsibilities: Help in reviewing charts of patients with nystagmus presenting prior to age 2 or 3 for a given period of time perhaps 3-5 years and create a database with MRI findings and demographics of these patients.

Will Waldrop, M.D. (PGY2)

Project: Survey of ophthalmologists' bilateral intravitreal injection practices. Collecting self-reported information about ophthalmologists' injection practices, including but not limited to the indications for same day bilateral injections, timing of performing second injections, when to inject only one eye, and others.

Brittany Ransom, M.D. (PGY4)

Project: Driving practices of the visually impaired. We will do patient surveys in the PMH eye clinic. Then, go to the EPIC chart to get more information about the patients, such as visual acuity, visual fields, and eye conditions.

Responsibilities: Assist with gathering info and entering into an Excel spreadsheet.

Deepak Ramesh, M.D. (PGY3)

Project: "The Effect of Orbicularis Resection on Upper Blepharoplasty". We are analyzing eyelid photos and video for Aston patients pre- and post-operatively to evaluate various parameters of eyelid contour, function, and a simple dry eye questionnaire. Need approximately 20-30 patients for this study.

Severin Pouly, M.D. (PGY3)

Project: A prospective randomized clinical study looking at the resident experience with the LenSx femtosecond laser in cataract surgery.

Responsibilities: Collect clinical data from EPIC and work with the PGY4 surgery chiefs to make sure all required data is collected during cataract sign-ups in the clinic. Duties may also involve helping administer patient surveys. This is anticipated to be at least a two-year project, so a student strongly interested in ophthalmology is ideal.

The student may go to the OR and help with data collection during/preoperatively/postoperatively cataract surgery. We are planning to enroll 180 patients in this study and each will have cataract surgery as part of the study.